CarlosAlonso,Manuel Soto
256
cell epitopes in themost variable region of the P2a, P2b and P0 proteins explains
the observed specificity of the response (69, 70). The P0 protein has been
employed in different vaccination assays in murine models of CL employing
susceptible (BALB/c) and resistant (C57BL/6) mice. BALB/c mice immunization
with a parasite P0-‐basedDNAvaccine orwith the rP0protein combinedwithTh1
inducing oligonucleotides inducedpartial protection after challengewith
L. major.
Immunized animals showed a delay in the development of cutaneous lesions but
miceultimatelydevelopedanon-‐healing formof thedisease (73, 74). On theother
hand, theTh1responses inducedbyvaccinationconferredprotectionagainst CL in
C57BL/6mice (74). Since theadministrationof someother ribosomal constituents
using immunization procedures inducing Th1 responses was related to the
generation of protective responses (75, 76), vaccines based on total ribosome
extract (LRP)were analyzed. In addition, a cDNAclone encoding the
L. braziliensis
ribosomal protein S4was recognizedby a T-‐cell clone derived froma resistant VL
humandonorwith a positiveDTHskin test (49), indicating that the recognitionof
some of the parasite ribosomal proteins by the host immune system is not
necessarily related to disease progression. Administration of the LRP combined
with Th1 inducing adjuvants prompted a ribosome-‐specific Th1 response inmice,
correlated with protection against the development of leishmaniasis due to
infective challengeswith
L. major
(77),
L. amazonensis
or
L. chagasi
(78) parasites.
The robust protection observed in the susceptible model BALB/c-‐
L. major
(detected by the absence of cutaneous lesions for long periods of time) was
accompanied by the capacity to resist a secondary infection (79). Two new
antigenic ribosomalmoleculesobtainedas recombinant proteinsby theexpression
of the
L. major
encoding LmL3 andLmL5 genes have shown immuno-‐prophylactic
propertiesagainst infectionwith
L.major
and
L. braziliensis
inBALB/cmice.
3.3. Leishmaniahomologofmammalianreceptor foractivatedCkinase(LACK)
LACK protein is one of the most studied Leishmania antigens. This
intracellular protein is amember of the tryptophan-‐aspartic acid repeat family of
proteins and it hasbeen implicated in the inductionof early IL-‐4 responses after L.
major infection(80). Inthis sense, BALB/c renderedtolerant toLACK, asaresult of
transgenic expression of this molecule in the thymus, were resistant to infection
withL. major anddevelop aTh1 response after infection (81). Several vaccination
protocols were tested in collaboration between Dr. Esteban (Centro Nacional de
Biotecnología) and Dr. Larraga (Centro de Investigaciones Biológicas) research
groups using different LACKpreparations, basedon the L. infantumLACKprotein,
thatwas characterized inDr. Larraga’s researchgroup (82). Themainstrategywas
the inductionof robust cellular responses against LACKby theuseof Th1 inducing
procedures (mainly DNA vaccines (83-‐85)) alone or combined with recombinant
Vaccinia virus expressing LACKusing a prime-‐boost strategy (86-‐94). Using these
